Our overall goal is to gain new information on the abnormal differentiation and function of leukemic cells and to establish better methods for the diagnosis and classification of acute leukemias. Major techniques to be applied are light (LM) and electron microscopy (EM) and cytochemistry, scanning EM, and tissue culture. We have established a firm theoretical and technical basis for the proposed research by our previous work on the differentiation and functions of normal leukocytes. Specifically, the objectives are: 1) to ascertain if defects in acute leukemia cell maturation correlate with "blocks in differentiation" at stages of the secretory pathway by analyzing the localization of peroxidase and other granule enzymes; 2) using LM, EM and histochemistry, to subclassify acute leukemias into distinct cell lines, with emphasis on developing and testing new methodologies; 3) to subclassify monocytic leukemias; 4) to test the theory that concurrent normal and abnormal (i.e., peroxidase-negative) PMN in the circulation may be helpful in diagnosing leukemia or pre-leukemia; 5) to examine the adherence of phagocytes to nylon wool by a new SEM technique on sheared cells to analyze temporal changes in microfilament patterns and degranulation; 6) to determine if acid phosphatase is a reliable marker enzyme for "T" cells; and 7) to study the in vitro differentiation of rat basophilic leukemia cells. This work on human leukemic cells should clarify aberrations in the step-wise assembly of their functional organelles during differentiation; more accurately define the cell-type(s) involved, thus permitting a precise correlation with protocols of therapy; allow a more reasonable, less empirical application of histochemical stains at the LM level for diagnosis; elucidate the cell pathology which increases the susceptibility to infection in leukemia; and finally, by investigating basic modes of cellular adherence to nylon wool, improve the procurement of leukocytes for transfusion.